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Direct evaluation of antiplatelet therapy in coronary artery disease by comprehensive image-based profiling of circulating platelets
Gabapentinoids confer survival benefit in human glioblastoma
Abstract Neuronal-glioma interactions are increasingly recognized as critical in the development and progression of central nervous system tumors. Recent research highlights that gliomas can integrate into neural circuits through various mechanisms, including the synaptogenic factor thrombospondin-1 (TSP-1). This new mechanistic understanding of cancer neuroscience allows for novel insights into target discovery. Critically, therapies that modulate neuron-tumor interactions remain agnostic to other oncogenic changes within tumor cells yet may still target fundamental drivers of tumor growth. In line with these findings and controlling for critical confounding variables, we demonstrate a survival benefit associated with gabapentin (an antagonist of TSP-1) following surgical resection of newly diagnosed glioblastoma. This retrospective, multi-institutional cohort study included 1,072 patients, with a discovery cohort of 693 patients and an additional 379 patients from a separate site for external validation. Furthermore, our findings indicate that gabapentin administration is associated with reduced serum TSP-1 levels, suggesting its potential as a future biomarker.
Bioinspired nondissipative mechanical energy storage and release in hydrogels via hierarchical sequentially swollen stretched chains
Abstract Nature suggests concepts for materials with efficient mechanical energy storage and release, i.e., resilience, involving small energy dissipation upon mechanical loading and unloading, such as in resilin and elastin. These materials facilitate burst-like movements involving high stiffness and low strain and high reversibility. Synthetic hydrogels that allow highly reversible mechanical energy storage have remained a challenge, despite mimicking biological soft tissues. Here we show a synthetic concept using fixed hydrogel polymer compositions based on sequentially swollen and sequentially photopolymerized gelation steps for hierarchical networks. The sequential swellings facilitate the balance of properties between resilience and dissipation upon controlling of the chain extension. At low hierarchical levels, we show resilience with small hysteresis with increased stiffness and resilient energy storage, whereas at high hierarchical levels, a transition is shown to a dissipative and considerably reinforced state. The generality of this approach is shown using several photopolymerizable monomers.
Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa
Abstract Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone. Whether combining antibiotics with phages may enhance effectiveness remains to be tested in experimental models. Here, we use a murine model of Pseudomonas -induced VAP to compare the efficacy of adjunctive phage cocktail for antibiotic therapy to either meropenem or phages alone. Combined treatment in murine VAP results in faster clinical improvement and prevents lung epithelial cell damage. Using human primary epithelial cells to dissect these synergistic effects, we find that adjunctive phage therapy reduces the minimum effective concentration of meropenem and prevents resistance development against both treatments. These findings suggest adjunctive phage therapy represents a promising treatment for MDR-induced VAP, enhancing the effectiveness of both antibiotics and phages while reducing adverse effects.
Building a unified model for drug synergy analysis powered by large language models
Glutamate gating of AMPA-subtype iGluRs at physiological temperatures
Label-free multimodal optical biopsy reveals biomolecular and morphological features of diabetic kidney tissue in 2D and 3D
Abstract Kidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities—stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)—within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, and lipid-protein concentrations previously unrecognized in kidney diseases. Using the same tissue section enhances diagnostic value without compromising limited tissue. These multimodal biomarkers broadly deepen the understanding of kidney disease progression by integrating lipidomic, fibrotic, and metabolic data.
Twist-programmable superconductivity in spin–orbit-coupled bilayer graphene
Long arcuate fascicle in wild and captive chimpanzees as a potential structural precursor of the language network
Abstract The arcuate fascicle (AF) is the main fibre tract in the brain for human language. It connects frontal and temporal language areas in the superior and middle temporal gyrus (MTG). The AF’s connection to the MTG was considered unique to humans and has influenced theories of the evolution of language. Here, using high-resolution diffusion MRI of post-mortem brains, we demonstrate that both wild and captive chimpanzees have a direct AF connection into the MTG, albeit weaker than in humans. This finding challenges the notion of a strictly human-specific AF morphology and suggests that language-related neural specialisation in humans likely evolved through gradual evolutionary strengthening of a pre-existing connection, rather than arising de novo. It is likely that this neural architecture supporting complex communication was already present in the last common ancestor of hominins and chimpanzees 7 million years ago, enabling the evolution of language processes in the human lineage.
How Korea’s female divers have adapted to cold plunges
Boosted high-throughput D⁺ transfer from D₂O to unsaturated bonds via Pdδ+ cathode for solvent-free deuteration
Abstract Deuterated organic compounds have gained significant attention due to their diverse applications, including reaction mechanism studies, probes for metabolism and pharmacokinetics, and raw materials for labeled compounds and polymers. Conventional reductive deuteration methods are limited by the high cost of deuterium sources (e.g., D₂ gas) and challenges in product separation and D₂O recycling. Electrochemical deuteration using D₂O is promising, but existing methods still suffer from low Faradaic efficiency (FE) and high separation costs. Herein, we report a deuterium ion diffusion-based all-solid electrolyser, featuring a RuO₂ anode for D+ generation from pure D2O and a Pd/nitrogen-doped carbon-based liquid diffusion cathode (Pdδ+/NC LDC) with tunable electron deficiencies Pdδ+/NC to enhance selective deuteration. This system achieves over 99% selectivity for deuterated benzyl alcohol with a FE of 72%, and demonstrates broad applicability for the deuteration of aldehydes, ketones, imines, and alkenes with high FE and selectivity. Moreover, the Pdδ+/NC-based electrolyser can achieve ten-gram-scale production of deuterated benzyl alcohol over 500 hours, showcasing its potential for high-throughput, solvent-free deuteration reactions in practical applications.
The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel
Superconductivity and spin canting in spin–orbit-coupled trilayer graphene
Enhanced coherence from correlated states in WSe2/MoS2 moiré heterobilayer
Photoexcited nitroarene-enabled carbon chain-elongated oxidation of alkenes via tandem oxidative cleavage and dipolar cycloaddition
Copper difluorocarbene-involved catalytic gem-difluoropropargylation
Extreme synchronization transitions
Abstract Across natural and human-made systems, transition points mark sudden changes of order and are thus key to understanding overarching system features. Motivated by recent experimental observations, we here uncover an intriguing class of transitions in coupled oscillators, extreme synchronization transitions, from asynchronous disordered states to synchronous states with almost completely ordered phases. Whereas such a transition appears like discontinuous or explosive phase transitions, it exhibits markedly distinct features. First, the transition occurs already in finite systems of N units and so constitutes an intriguing bifurcation of multi-dimensional systems rather than a genuine phase transition that emerges in the thermodynamic limit N → ∞ only. Second, the synchronization order parameter jumps from moderate values of the order of N −1/2 to values extremely close to 1, its theoretical maximum, immediately upon crossing a critical coupling strength. We analytically explain the mechanisms underlying such extreme transitions in coupled complexified Kuramoto oscillators. Extreme transitions may similarly occur across other systems of coupled oscillators as well as in certain percolation processes. In applications, their occurrence impacts our ability of ensuring or preventing strong forms of ordering, for instance in biological and engineered systems.